Coates, B. M., Staricha, K. L., Wiese, K. M. & Ridge, K. M. Influenza A Virus Infection, Innate Immunity, and Childhood. JAMA Pediatr. 169, 956–963 (2015).
Petrova, V. N. & Russell, C. A. The evolution of seasonal influenza viruses. Nat. Rev. Microbiol. 16, 47–60 (2018).
Roberts, N. J., Jr. & Krilov, L. R. The Continued Threat of Influenza A Viruses. Viruses 14, https://doi.org/10.3390/v14050883 (2022).
Heaton, N. S., Sachs, D., Chen, C. J., Hai, R. & Palese, P. Genome-wide mutagenesis of influenza virus reveals unique plasticity of the hemagglutinin and NS1 proteins. Proc. Natl Acad. Sci. USA 110, 20248–20253 (2013).
Vincent, A. et al. Review of influenza A virus in swine worldwide: a call for increased surveillance and research. Zoonoses Public Health 61, 4–17 (2014).
Vincent, A. L., Lager, K. M. & Anderson, T. K. Animal Influenza Virus. 243–258 (Springer, 2014).
Howley, P. M. et al. Fields Virology. 7 edn, Vol. 1, 596–705 (Wolters Kluwer, 2021).
Nelli, R. K. et al. Comparative distribution of human and avian type sialic acid influenza receptors in the pig. BMC Vet. Res. 6, 4 (2010).
Ito, T. et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J. Virol. 72, 7367–7373 (1998).
Van Kerkhove, M. D., Hirve, S., Koukounari, A., Mounts, A. W. & group, H. N. p. s. w. Estimating age-specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries. Influenza Other Respir. Viruses 7, 872–886 (2013).
Dawood, F. S. et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect. Dis. 12, 687–695 (2012).
CDC. Prioritizing Zoonotic Diseases for Multisectoral, One Health Collaboration in the United States. https://www.cdc.gov/onehealth/pdfs/us-ohzdp-report-508.pdf (2018).
CDC. Reported Infections with Variant Influenza Viruses in the United States since 2005. https://www.cdc.gov/flu/swineflu/variant-cases-us.htm (2017).
Donovan, T. S. Influenza isolate selection methodology for timely autogenous vaccine use. Proceedings. Amer Assoc Swine Vet Conf, 557–561 (2008).
Cornelison, A. S. et al. Impact of health challenges on pig growth performance, carcass characteristics, and net returns under commercial conditions. Transl. Anim. Sci. 2, 50–61 (2018).
Walia, R. R., Anderson, T. K. & Vincent, A. L. Regional patterns of genetic diversity in swine influenza A viruses in the United States from 2010 to 2016. Influenza Other Respir. Viruses 13, 262–273 (2019).
Anderson, T. K. et al. Swine Influenza A Viruses and the Tangled Relationship with Humans. Cold Spring Harb. Perspect. Med. 11, https://doi.org/10.1101/cshperspect.a038737 (2021).
Lewis, N. S. et al. The global antigenic diversity of swine influenza A viruses. Elife 5, e12217 (2016).
Jang, Y., Seo, T. & Seo, S. H. Higher virulence of swine H1N2 influenza viruses containing avian-origin HA and 2009 pandemic PA and NP in pigs and mice. Arch. Virol. 165, 1141–1150 (2020).
Shope, R. E. Swine Influenza: Iii. Filtration Experiments and Etiology. J. Exp. Med. 54, 373–385 (1931).
Brown, I. H., Chakraverty, P., Harris, P. A. & Alexander, D. J. Disease outbreaks in pigs in Great Britain due to an influenza A virus of H1N2 subtype. Vet. Rec. 136, 328–329 (1995).
Guan, Y. et al. Emergence of avian H1N1 influenza viruses in pigs in China. J. Virol. 70, 8041–8046 (1996).
Anderson, T. K. et al. A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses. mSphere 1, https://doi.org/10.1128/mSphere.00275-16 (2016).
Lorusso, A. et al. Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008. J. Gen. Virol. 92, 919–930 (2011).
Sandbulte, M. R., Spickler, A. R., Zaabel, P. K. & Roth, J. A. Optimal Use of Vaccines for Control of Influenza A Virus in Swine. Vaccines 3, 22–73 (2015).
Herrera-Rodriguez, J., Signorazzi, A., Holtrop, M., de Vries-Idema, J. & Huckriede, A. Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production. Vaccine 37, 1630–1637 (2019).
Bourne, F. J. & Curtis, J. The transfer of immunoglobins IgG, IgA and IgM from serum to colostrum and milk in the sow. Immunology 24, 157–162 (1973).
Pyo, H. M., Hlasny, M. & Zhou, Y. Influence of maternally-derived antibodies on live attenuated influenza vaccine efficacy in pigs. Vaccine 33, 3667–3672 (2015).
Rajao, D. S. et al. Heterologous challenge in the presence of maternally-derived antibodies results in vaccine-associated enhanced respiratory disease in weaned piglets. Virology 491, 79–88 (2016).
Abente, E. J. et al. Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses. J. Virol. 92, https://doi.org/10.1128/JVI.01323-18 (2018).
Gauger, P. C. et al. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (delta-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus. Vaccine 29, 2712–2719 (2011).
Gauger, P. C. et al. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus. Vet. Pathol. 49, 900–912 (2012).
Khurana, S. et al. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease. Sci. Transl. Med. 5, 200ra114 (2013).
Moraes, D. C. A. et al. Veterinarian perceptions and practices in prevention and control of influenza virus in the Midwest United States swine farms. Front. Vet. Sci. 10, 1089132 (2023).
Erdman, M. M., Kamrud, K. I., Harris, D. L. & Smith, J. Alphavirus replicon particle vaccines developed for use in humans induce high levels of antibodies to influenza virus hemagglutinin in swine: proof of concept. Vaccine 28, 594–596 (2010).
Vander Veen, R. et al. Rapid development of an efficacious swine vaccine for novel H1N1. PLoS Curr. 1, RRN1123 (2009).
Vander Veen, R. L. et al. Safety, immunogenicity, and efficacy of an alphavirus replicon-based swine influenza virus hemagglutinin vaccine. Vaccine 30, 1944–1950 (2012).
Vander Veen, R. L. et al. Haemagglutinin and nucleoprotein replicon particle vaccination of swine protects against the pandemic H1N1 2009 virus. Vet. Rec. 173, 344 (2013).
Wymore Brand, M. et al. Bivalent hemagglutinin and neuraminidase influenza replicon particle vaccines protect pigs against influenza a virus without causing vaccine associated enhanced respiratory disease. Vaccine 40, 5569–5578 (2022).
Bosworth, B. et al. Replicon particle vaccine protects swine against influenza. Comp. Immunol. Microbiol. Infect. Dis. 33, e99–e103 (2010).
Petro-Turnquist, E., Pekarek, M. J. & Weaver, E. A. Swine influenza A virus: challenges and novel vaccine strategies. Front. Cell Infect. Microbiol. 14, 1336013 (2024).
Zeller, M. A., Anderson, T. K., Walia, R. W., Vincent, A. L. & Gauger, P. C. ISU FLUture: a veterinary diagnostic laboratory web-based platform to monitor the temporal genetic patterns of Influenza A virus in swine. BMC Bioinforma. 19, 397 (2018).
Theiler, J. & Korber, B. Graph-based optimization of epitope coverage for vaccine antigen design. Stat. Med. 37, 181–194 (2018).
Theiler, J. et al. Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci. Rep. 6, 33987 (2016).
Coudeville, L. et al. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model. BMC Med. Res. Methodol. 10, 18 (2010).
Black, S. et al. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr. Infect. Dis. J. 30, 1081–1085 (2011).
Hobson, D., Curry, R. L., Beare, A. S. & Ward-Gardner, A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J. Hyg. 70, 767–777 (1972).
Gooch, K. E. et al. Heterosubtypic cross-protection correlates with cross-reactive interferon-gamma-secreting lymphocytes in the ferret model of influenza. Sci. Rep. 9, 2617 (2019).
Vatzia, E. et al. Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs. NPJ Vaccines 8, 19 (2023).
Tchilian, E. & Holzer, B. Harnessing Local Immunity for an Effective Universal Swine Influenza Vaccine. Viruses 9, https://doi.org/10.3390/v9050098 (2017).
Hillaire, M. L. B. et al. Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells. J. Gen. Virol. 92, 2339–2349 (2011).
Lehtinen, M., Hibma, M. H., Stellato, G., Kuoppala, T. & Paavonen, J. Human T helper cell epitopes overlap B cell and putative cytotoxic T cell epitopes in the E2 protein of human papillomavirus type 16. Biochem. Biophys. Res Commun. 209, 541–546 (1995).
Detmer, S. E. Animal Influenza. Vol. 1 435–451 (John Wiley & Sons, Inc, 2016).
Pomorska-Mol, M. et al. Immune and inflammatory response in pigs during acute influenza caused by H1N1 swine influenza virus. Arch. Virol. 159, 2605–2614 (2014).
Van Reeth, K., Van Gucht, S. & Pensaert, M. In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding. Vet. Immunol. Immunopathol. 87, 161–168 (2002).
Barbe, F., Saelens, X., Braeckmans, D., Lefevre, F. & Reeth, K. V. Role of IFN-alpha during the acute stage of a swine influenza virus infection. Res Vet. Sci. 88, 172–178 (2010).
Turlewicz-Podbielska, H., Czyzewska-Dors, E. & Pomorska-Mol, M. Respiratory viral infections drive different lung cytokine profiles in pigs. BMC Vet. Res. 17, 5 (2021).
USDA. Influenza a virus in swine surveillance quarterly report for fiscal year 2022, https://www.aphis.usda.gov/animal_health/animal_dis_spec/swine/downloads/fy2022quarter3swinereport.pdf (2021).
CDC. Prioritizing zoonotic diseases for multisectoral, one health collaboration in the united states (2018) (CDC, 2018).
USDA. The biological hog cycle, https://www.ers.usda.gov/topics/animal-products/hogs-pork/sector-at-a-glance/#:~:text=In%20a%20farrow-to-finish%20operation%2C%2022-26%20weeks%20%28starting%20at,This%20is%20the%20farrow-to-wean%20phase%20of%20hog%20production (2022).
Chen, M. W. et al. A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc. Natl Acad. Sci. USA 105, 13538–13543 (2008).
Laddy, D. J., Yan, J., Corbitt, N., Kobinger, G. P. & Weiner, D. B. Immunogenicity of novel consensus-based DNA vaccines against avian influenza. Vaccine 25, 2984–2989 (2007).
Wu, P. et al. Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses. Front. Immunol. 8, 1649 (2017).
Sun, H., Sur, J. H., Sillman, S., Steffen, D. & Vu, H. L. X. Design and characterization of a consensus hemagglutinin vaccine immunogen against H3 influenza A viruses of swine. Vet. Microbiol 239, 108451 (2019).
Bullard, B. L. & Weaver, E. A. Strategies Targeting Hemagglutinin as a Universal Influenza Vaccine. Vaccines 9, https://doi.org/10.3390/vaccines9030257 (2021).
Carter, D. M. et al. Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses. J. Virol. 90, 4720–4734 (2016).
Sautto, G. A. et al. A Computationally Optimized Broadly Reactive Antigen Subtype-Specific Influenza Vaccine Strategy Elicits Unique Potent Broadly Neutralizing Antibodies against Hemagglutinin. J. Immunol. 204, 375–385 (2020).
Allen, J. D., Jang, H., DiNapoli, J., Kleanthous, H. & Ross, T. M. Elicitation of Protective Antibodies against 20 Years of Future H3N2 Cocirculating Influenza Virus Variants in Ferrets Preimmune to Historical H3N2 Influenza Viruses. J. Virol. 93, https://doi.org/10.1128/JVI.00946-18 (2019).
Wong, T. M. et al. Computationally Optimized Broadly Reactive Hemagglutinin Elicits Hemagglutination Inhibition Antibodies against a Panel of H3N2 Influenza Virus Cocirculating Variants. J. Virol. 91, https://doi.org/10.1128/JVI.01581-17 (2017).
Giles, B. M., Bissel, S. J., Dealmeida, D. R., Wiley, C. A. & Ross, T. M. Antibody breadth and protective efficacy are increased by vaccination with computationally optimized hemagglutinin but not with polyvalent hemagglutinin-based H5N1 virus-like particle vaccines. Clin. Vaccin. Immunol. 19, 128–139 (2012).
Giles, B. M. et al. A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection. J. Infect. Dis. 205, 1562–1570 (2012).
Nunez, I. A. & Ross, T. M. Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses. Vaccine 38, 830–839 (2020).
Ross, T. M. et al. A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains. Vaccine 37, 2369–2376 (2019).
Skarlupka, A. L. et al. Computationally optimized broadly reactive vaccine based upon swine H1N1 influenza hemagglutinin sequences protects against both swine and human isolated viruses. Hum. Vaccin Immunother. 15, 2013–2029 (2019).
Bullard, B. L. et al. Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus. Nat. Commun. 12, 1203 (2021).
Hulot, S. L. et al. Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost. J. Virol. 89, 6462–6480 (2015).
Gutierrez, A. H. et al. In Vivo Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model. PLoS One 11, e0159237 (2016).
Hitt, M. M., Addison, C. L., Graham, F. L. Human adenovirus vectors for gene transfer into mammalian cells. Adv. Pharm. 40, 137–206 (1997).
Ferreira, R. G., Gordon, N. F. & Stock, R. & Petrides, D. Adenoviral Vector COVID-19 Vaccines: Process and Cost Analysis. MDPI Processes 8, https://doi.org/10.3390/pr9081430 (2021).
Wesley, R. D. & Lager, K. M. Overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus. Vet. Microbiol. 118, 67–75 (2006).
Buchbinder, S. P. et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372, 1881–1893 (2008).
Casimiro, D. R. et al. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene. J. Virol. 77, 6305–6313 (2003).
Barouch, D. H. et al. Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. J. Immunol. 172, 6290–6297 (2004).
Petro-Turnquist, E. M., Bullard, B. L., Pekarek, M. J. & Weaver, E. A. Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection against H2 Influenza a Virus. Vaccines 10, https://doi.org/10.3390/vaccines10060926 (2022).
Lee, B. W., Bey, R. F., Baarsch, M. J. & Larson, M. E. Class specific antibody response to influenza A H1N1 infection in swine. Vet. Microbiol. 43, 241–250 (1995).
Larsen, D. L., Karasin, A., Zuckermann, F. & Olsen, C. W. Systemic and mucosal immune responses to H1N1 influenza virus infection in pigs. Vet. Microbiol. 74, 117–131 (2000).
Renegar, K. B., Small, P. A. Jr., Boykins, L. G. & Wright, P. F. Role of IgA versus IgG in the control of influenza viral infection in the murine respiratory tract. J. Immunol. 173, 1978–1986 (2004).
Heinen, P. P., van Nieuwstadt, A. P., de Boer-Luijtze, E. A. & Bianchi, A. T. Analysis of the quality of protection induced by a porcine influenza A vaccine to challenge with an H3N2 virus. Vet. Immunol. Immunopathol. 82, 39–56 (2001).
Larsen, D. L. & Olsen, C. W. Effects of DNA dose, route of vaccination, and coadministration of porcine interleukin-6 DNA on results of DNA vaccination against influenza virus infection in pigs. Am. J. Vet. Res. 63, 653–659 (2002).
Romagosa, A. et al. Vaccination of influenza a virus decreases transmission rates in pigs. Vet. Res. 42, 120 (2011).
Edmans, M. et al. Magnitude and Kinetics of T Cell and Antibody Responses During H1N1pdm09 Infection in Inbred Babraham Pigs and Outbred Pigs. Front. Immunol. 11, 604913 (2020).
Lager, K. M. & Vincent, A. L. In Vivo Models for Pathotyping and Vaccine Efficacy for Swine Influenza. Methods Mol. Biol. 2123, 345–351 (2020).
Gauger, P. C. et al. Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease. Virology 471-473, 93–104 (2014).
Halbur, P. G. et al. Comparison of the pathogenicity of two US porcine reproductive and respiratory syndrome virus isolates with that of the Lelystad virus. Vet. Pathol. 32, 648–660 (1995).
Gauger, P. C. & Vincent, A. L. Enzyme-Linked Immunosorbent Assay for Detection of Serum or Mucosal Isotype-Specific IgG and IgA Whole-Virus Antibody to Influenza A Virus in Swine. Methods Mol. Biol. 2123, 311–320 (2020).